Triethylamine → 1-{[3,5-Bis(trifluoromethyl)phenyl]methyl}-3-phenylpiperazine

To a solution of 2-phenylpiperazine (4.0 gram, 24.65 mmol) in dry CH2 Cl2 (200 ml) at -78° C. under nitrogen was added Et3N (5.15 ml, 36.97 mmol) followed by the dropwise addition of a CH2 Cl2 solution(46.60 ml) of bis(trifluoromethyl)benzyl bromide (4.66 ml, 24.65 mmol). The flask was kept at -78° C. then it was gradually warmed to room temperature overnight. After TLC showed that the reaction was complete, the material was washed with brine (150 ml, 2×), dried over MgSO4, filtered, and evaporated under vacuum to yield a tan solid. The crude product was purified by flash silica gel chromatography (150 g), eluting with 2.5% MeOH/CH2Cl2 to give (±) 1-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-phenyl-piperazine (6.96 gram, 17.92 mmol, 72.7%) as an oil. A portion of this oil (0.5 gram, 1.287 mmol)) was converted to its hydrochloride salt by dissolving the oil in CH2Cl2 (20 ml) and treating with 2.3M HCl-EtOH (1.3 ml, 2.99 mmol). After stirring at room temperature for 10 minutes, all solvents were removed under high vacuum and the residue was dried overnight, m.p. 229°-233° C.; FAB mass [M+1]+ 389;

1. customwas kept at -78° C.
2. washthe material was washed with brine (150 ml, 2×)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. customevaporated under vacuum
6. customto yield a tan solid
7. customThe crude product was purified by flash silica gel chromatography (150 g)
8. washeluting with 2.5% MeOH/CH2Cl2

ORD record

ord-c328611ae7a14464bb2ed054959c38d3

Source dataset

uspto-grants-1998_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05719156